Differential neurostimulation therapy driven by physiological therapy

ABSTRACT

An implantable neurostimulator system adapted to provide therapy for various neurological disorders is capable of varying therapy delivery strategies based on the context, physiological or otherwise, into which the therapy is to be delivered. Responsive and scheduled therapies can be varied depending on various sensor measurements, calculations, inferences, and device states (including elapsed times and times of day) to deliver an appropriate course of therapy under the circumstances.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation application of and claims the benefit ofco-pending U.S. patent application Ser. No. 13/523,855, filed on Jun.14, 2012, entitled “Differential Neurostimulation Therapy Driven ByPhysiological Therapy” by Pless et al., which is a continuationapplication of and claims the benefit of U.S. patent application Ser.No. 13/109,970, now U.S. Pat. No. 8,224,452, filed on May 17, 2011,which is a continuation of and claims the benefit of U.S. patentapplication Ser. No. 11/436,191, now U.S. Pat. No. 7,966,073, filed onMay 16, 2006, which is a continuation of and claims the benefit of U.S.patent application Ser. No. 10/121,933 filed on Apr. 12, 2002, nowabandoned, which is a continuation-in-part of and claims the benefit ofU.S. patent application Ser. No. 09/962,940, now U.S. Pat. No.6,480,743, filed on Sep. 24, 2001, which in turn is acontinuation-in-part of and claims the benefit of U.S. patentapplication Ser. No. 09/543,264 filed on Apr. 5, 2000, now U.S. Pat. No.6,944,501, and is also a continuation-in-part of and claims the benefitof U.S. patent application Ser. No. 09/543,450 also filed on Apr. 5,2000, now U.S. Pat. No. 6,466,822, which are all incorporated herein byreference in their entirety. All of the aforementioned applicationsand/or patents are assigned to the assignee of the present application.

FIELD

The disclosed embodiments relate to electrical stimulation therapy forneurological disorders, and more particularly to applying differenttypes of therapy to treat different types of neurological events.

BACKGROUND

Epilepsy, a neurological disorder characterized by the occurrence ofseizures (specifically episodic impairment or loss of consciousness,abnormal motor phenomena, psychic or sensory disturbances, or theperturbation of the autonomic nervous system), is debilitating to agreat number of people. It is believed that as many as two to fourmillion Americans may suffer from various forms of epilepsy. Researchhas found that its prevalence may be even greater worldwide,particularly in less economically developed nations, suggesting that theworldwide figure for epilepsy sufferers may be in excess of one hundredmillion.

Because epilepsy is characterized by seizures, its sufferers arefrequently limited in the kinds of activities they may participate in.Epilepsy can prevent people from driving, working, or otherwiseparticipating in much of what society has to offer. Some epilepsysufferers have serious seizures so frequently that they are effectivelyincapacitated.

Furthermore, epilepsy is often progressive and can be associated withdegenerative disorders and conditions. Over time, epileptic seizuresoften become more frequent and more serious, and in particularly severecases, are likely to lead to deterioration of other brain functions(including cognitive function) as well as physical impairments.

The current state of the art in treating neurological disorders,particularly epilepsy, typically involves drug therapy and surgery. Thefirst approach is usually drug therapy.

A number of drugs are approved and available for treating epilepsy, suchas sodium valproate, phenobarbital/primidone, ethosuximide, gabapentin,phenytoin, and carbamazepine, as well as a number of others.Unfortunately, those drugs typically have serious side effects,especially toxicity, and it is extremely important in most cases tomaintain a precise therapeutic serum level to avoid breakthroughseizures (if the dosage is too low) or toxic effects (if the dosage istoo high). The need for patient discipline is high, especially when apatient's drug regimen causes unpleasant side effects the patient maywish to avoid.

Moreover, while many patients respond well to drug therapy alone, asignificant number (at least 20-30%) do not. For those patients, surgeryis presently the best-established and most viable alternative course oftreatment.

Currently practiced surgical approaches include radical surgicalresection such as hemispherectomy, corticectomy, lobectomy and partiallobectomy, and less-radical lesionectomy, transection, and stereotacticablation. Besides being less than fully successful, these surgicalapproaches generally have a high risk of complications, and can oftenresult in damage to eloquent (i.e., functionally important) brainregions and the consequent long-term impairment of various cognitive andother neurological functions. Furthermore, for a variety of reasons,such surgical treatments are contraindicated in a substantial number ofpatients. And unfortunately, even after radical brain surgery, manyepilepsy patients are still not seizure-free.

Electrical stimulation is an emerging therapy for treating epilepsy.However, currently approved and available electrical stimulation devicesapply continuous electrical stimulation to neural tissue surrounding ornear implanted electrodes, and do not perform any detection—they are notresponsive to relevant neurological conditions.

The NeuroCybernetic Prosthesis (NCP) from Cyberonics, for example,applies continuous electrical stimulation to the patient's vagus nerve.This approach has been found to reduce seizures by about 50% in about50% of patients. Unfortunately, a much greater reduction in theincidence of seizures is needed to provide clinical benefit. The Activadevice from Medtronic is a pectorally implanted continuous deep brainstimulator intended primarily to treat Parkinson's disease; it has alsobeen tested for epilepsy. In operation, it supplies a continuouselectrical pulse stream to a selected deep brain structure where anelectrode has been implanted.

Continuous stimulation of deep brain structures for the treatment ofepilepsy has not met with consistent success. To be effective interminating seizures, it is believed that one effective site wherestimulation should be performed is near the focus of the epileptogenicregion of the brain. The focus is often in the neocortex, wherecontinuous stimulation may cause significant neurological deficit withclinical symptoms including loss of speech, sensory disorders; orinvoluntary motion. Accordingly, research has been directed towardautomatic responsive epilepsy treatment based on a detection of imminentseizure.

The episodic attacks or seizures experienced by a typical epilepsypatient are characterized by periods of abnormal neurological activity.“Epileptiform” activity refers to specific neurological activityassociated with epilepsy as well as with an epileptic seizure and itsprecursors; such activity is frequently manifested in electrographicsignals in the patient's brain.

Most prior work on the detection and responsive treatment of seizuresvia electrical stimulation has focused on analysis ofelectroencephalogram (EEG) and electrocorticogram (ECoG) waveforms. Ingeneral, EEG signals represent aggregate neuronal activity potentialsdetectable via electrodes applied to a patient's scalp, and ECoGs useinternal electrodes near the surface of or within the brain. ECoGsignals, deep-brain counterparts to EEG signals, are detectable viaelectrodes implanted on the dura mater, under the dura mater, or viadepth electrodes (and the like) within the patient's brain. Unless thecontext clearly and expressly indicates otherwise, the term “EEG” shallbe used generically herein to refer to both EEG and ECoG signals.

It is generally preferable to be able to detect and treat a seizure ator near its beginning, or even before it begins. The beginning of aseizure is referred to herein as an “onset.” However, it is important tonote that there are two general varieties of seizure onsets. A “clinicalonset” represents the beginning of a seizure as manifested throughobservable clinical symptoms, such as involuntary muscle movements orneurophysiological effects such as lack of responsiveness. An“electrographic onset” refers to the beginning of detectableelectrographic activity indicative of a seizure. An electrographic onsetwill frequently occur before the corresponding clinical onset, enablingintervention before the patient suffers symptoms, but that is not alwaysthe case. In addition, there often are perceptible changes in the EEG,or “precursors,” that occur seconds or even minutes before theelectrographic onset that can be identified and used to facilitateintervention before electrographic or clinical onsets occur. Thiscapability would be considered seizure prediction, in contrast to thedetection of a seizure or its onset.

It has been suggested that it is possible to treat and terminateseizures by applying specific responsive electrical stimulation signalsto the brain. See, e.g., U.S. Pat. No. 6,016,449 to Fischel) et al., H.R. Wagner, et al., Suppression of Cortical Epileptiform Activity byGeneralized and Localized ECoG Desynchronization, Electroencephalogr.Clin. Neurophysiol. 1975; 39(5): 499-506; and R. P. Lesser et al., BriefBursts of Pulse Stimulation Terminate Afterdischarges Caused by CorticalStimulation, Neurology 1999; 53(December): 2073-81. Unlike thecontinuous stimulation approaches, described above, responsivestimulation is intended to be performed only when a seizure (or otherundesired neurological event) is occurring or about to occur. Thisapproach is believed to be preferable to continuous or semi-continuousstimulation, as stimulation at inappropriate times and quantities may)result in the initiation of seizures, an increased susceptibility toseizures, or other undesired side effects. Responsive stimulation, onthe other hand, tends to avoid side effects, to avoid undesiredhabituating and conditioning (learning) effects on the brain, and toprolong the battery life of an implantable device.

While responsive stimulation alone is considered an advantageous therapyfor seizures, it is believed possible to further reduce the incidence ofseizures by applying continuous or periodic scheduled stimulation tocertain parts of the brain while also performing responsive electricalstimulation as described above. See, for example, U.S. patentapplication Ser. No. 09/543,450 filed on Apr. 5, 2000; U.S. Pat. No.5,683,422 to Rise; and I. S. Cooper et al., “Effects of CerebellarStimulation on Epilepsy, the EEG and Cerebral. Palsy in Man,”Electroencephalogr. Clin. Neurophysiol. 1978; 34: 349-54. Drug therapy,either continuous or applied by an implantable device upon demand or ona schedule, is also believed to be a useful adjunct to responsive andprogrammed electrical stimulation.

Current approaches to responsive stimulation have certain obviousdrawbacks. In general, the need to apply responsive therapy indicatesthat a seizure or other event is imminent or already occurring, whichmight have adverse implications for the patient. Accordingly, it wouldbe preferable to be able to detect events and conditions that precedeseizures and treat them less aggressively, thereby discouraging theseizure from ever occurring.

Moreover, seizures (and other events) and their onsets almost alwaysdiffer in some way—with different types, locations, and characteristicsin different individuals, and also frequently between multiple events inthe same individual. Finally, it should be recognized that certaintreatments, and specifically certain kinds of stimulation might not workwell for all of a patient's seizures, and in some cases, might evenexacerbate some seizures. A Boolean responsive treatment strategy (i.e.,a choice between applying one kind of therapy and not applying therapyat all) may not be effective in certain patients, and does not providemuch of a structured course of treatment for episodes of varyingseverity.

Accordingly, and for the reasons set forth above, it is desirable to beable to apply the best possible therapy for each of a patient's episodesof epileptiform activity or other symptoms. Such therapy would have anincreased chance of disrupting epileptiform activity, thereby avoiding,terminating, or lessening the severity of the patient's seizuredisorder.

SUMMARY

The disadvantages of traditional and known approaches to electricalstimulation for epilepsy, including certain approaches to responsivestimulation, are ameliorated by the embodiments described herein.Generally, the disclosed embodiments provide responsive therapy forepilepsy and other neurological disorders, namely, therapy that isresponsive to detected electrographic patterns, electrophysiologicalconditions, and other physiological conditions capable of being observedand identified through implanted sensors.

Various embodiments are capable of providing differential therapy basedon a detected event type or other neurological or physiological context,thereby providing certain advantages over basic electricalneurostimulation therapy and responsive neurostimulation in general.

The different types of therapies deliverable by a system according tosome embodiments can be based upon any of a number of different factors,including the type of onset, seizure, or other event detected; thelocation of the onset, seizure, or other event detected; the morphologyor frequency content of the ECoG during the onset, seizure, or otherevent detected; whether the seizure or other event has generalized orpropagated through the patient's brain; whether the patient is asleep orawake; and any other possible relevant electrophysiological or othercharacteristic (e.g., observed via an implanted sensor) of the patient,considered alone or in combination with detected events described above.Differing treatment approaches might also be affected by a state of thesystem (and in particular, the implantable device), and whether othertreatments have recently been applied or are about to be applied.

The various treatment approaches offered by a system according to thedisclosed embodiments are effective to avoid or stop an onset of aseizure or other neurological event, to halt the propagation of anexisting seizure or neurological event, to reduce the susceptibility ofa patient to seizures or other undesired symptoms or effects, or to warna patient, caregiver, or physician of the patient's condition. Thesestrategies and others will be apparent in connection with the detaileddescription set forth below.

Various different electrical stimulation approaches are possible. Forexample, and as treated in detail in U.S. Pat. No. 6,016,449 to Fischel)et al. and elsewhere, responsive stimulation can be applied at or nearthe focus of epileptiform activity. It may also be efficacious incertain circumstances to apply stimulation to a functionally relevantbrain structure, either on a patient-specific basis (e.g., structuresand pathways in communication with a seizure focus, lesion site, orother feature of interest, as described in U.S. patent application Ser.No. 09/724,805, filed on Nov. 28, 2000, which is hereby incorporated byreference as though set forth in full herein) or at a predetermined siteknown or suspected to have a role (e.g., the caudate nucleus, describedin greater detail below). There are, of course, other possibilities thatwill be apparent to a practitioner of ordinary skill in the art.

Alternative therapies are also possible and are usable in variousembodiments, including on-demand drug dispensing; audio, sensory, andsomatosensory stimulation; and other approaches.

It will be appreciated that contextual information observed at the timeof a neurological event of interest can be used in at least two ways. Inconnection with the embodiments described herein, such information canbe used to determine the nature of the neurological event and hence whattype of therapy (and how and where delivered) would be most effective.It is also possible to use information to provide adaptive therapyvariations, in the manner described in U.S. patent application Ser. No.09/962,940, of which the present disclosure is a continuation-in-part.The two approaches are not mutually exclusive, and as described below,can be used together.

Accordingly, a system in some embodiments generally includes animplantable neurostimulator capable of interfacing with externalequipment, a detection subsystem capable of detecting a neurologicalevent of interest in the patient and measuring or otherwise observingsome characteristic of the neurological event, and a therapy subsystemcapable of treating the patient by varying its treatment approach basedon the observed characteristic. As used herein, the term therapy appliesnot only to a treatment intended to treat an emergent condition, butalso to a prophylactic treatment intended to reduce the likelihood of acondition occurring.

Generally, various embodiments may be performed by measuring acharacteristic of a detected neurological event, as described above,transforming or modifying a parameter associated with thecharacteristic, and using the parameter to select and transform adesired therapy that is deemed appropriate and effective given thenature of the event.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other objects, features, and advantages will become apparentfrom the detailed description below and the accompanying drawings, inwhich:

FIG. 1 is a schematic illustration of a patient's cranium showing theplacement of an implantable neurostimulator according to an embodiment,including leads extending to the patient's brain;

FIG. 2 is a block diagram illustrating a context in which an implantableneurostimulator according to an embodiment is implanted and operated,including various items of external equipment;

FIG. 3 is a block diagram illustrating the major functional subsystemsof an implantable neurostimulator according to an embodiment;

FIG. 4 is a block diagram illustrating the functional components of thedetection subsystem of the implantable neurostimulator shown in FIG. 3;

FIG. 5 is a block diagram illustrating the functional components of thetherapy subsystem of the implantable neurostimulator shown in FIG. 3;

FIG. 6 illustrates several possible electrical stimulation modalitiesaccording to an embodiment;

FIG. 7 is a flow chart illustrating a device-context-based approach todifferential therapy according to an embodiment;

FIG. 8 is a flow chart illustrating a physiological-context-basedapproach to differential therapy according to an embodiment;

FIG. 9 is a flow chart illustrating the process performed by a systemaccording to an embodiment in obtaining information about an event typefrom detection data stored by an implantable neurostimulator accordingto an embodiment;

FIG. 10 is a flow chart illustrating the process performed by a systemaccording to some embodiments in obtaining information about an eventtype from electrophysiology measurement data stored or otherwiseacquired by an implantable neurostimulator according to an embodiment;and

FIG. 11 is a flow chart illustrating the process performed by a systemaccording to an embodiment in obtaining information about an event typefrom sensor measurement data stored or otherwise acquired by animplantable neurostimulator according to an embodiment.

DETAILED DESCRIPTION

Various embodiments are described below, with reference to detailedillustrative embodiments. It will be apparent that a system according tothe invention may be embodied in a wide variety of forms. Consequently,the specific structural and functional details disclosed herein arerepresentative and do not limit the scope of the invention.

In various embodiments, differential therapy is provided, that is,treatments that are tailored to the types and characteristics ofseizures and other neurological events experienced by patients. This isaccomplished by measuring or otherwise observing a characteristic of theevent—typically the nature of a seizure onset, including its type,morphology, location, or other properties—and selecting and delivering acourse of therapy accordingly. In addition, some embodiments usedifferential therapy applied prophylactically whereby treatments aretailored to characteristics of predictive events that generally precedeneurological events, and where applying such tailored treatments isintended to reduce the likelihood of the neurological event occurring.

A determination as to what type of therapy to apply can be based uponmany possible measurements and observations, several of which will bedescribed in detail below (though other possibilities will be apparentto those of skill in the art of treating epilepsy and other neurologicaldisorders with electrical stimulation and other therapies). Inparticular, various parameters can be measured at the time of a detectedevent, or before or after the event. In some embodiments, the systemsand methods are not limited to single measurements, as trends andhistorical changes in neurological conditions, including (for purposesof illustration) but not limited to EEG activity, electrophysiologicalconditions, and neurotransmitter levels, can be observed and might, insome embodiments, guide treatment.

One neurological event characteristic that is particularly relevant totreatment is the type of seizure onset experienced by a patient. It hasbeen found that single patients can experience multiple types ofseizures at different times, and also that certain types of seizureonsets respond well to certain types of therapies, and that other typesof onsets do not.

For a general description of several different onset types, see, e.g.,S. Spencer et al., “Morphological Patterns of Seizures RecordedIntracranially,” Epilepsia, 33(3): 537-45 (1992); and S.-A. Lee et al.,“Intracranial EEG Seizure-Onset Patterns in Neocortical Epilepsy,”Epilepsia, 41(3): 297-307 (2000).

Seizure onset types can often be characterized at least in part by theirEEG morphologies. In particular, and by way of example, two commonseizure onset types are characterized by distinctly different EEGpatterns. A first type of seizure onset is defined by and includesquasi-sinusoidal, or relatively rounded, EEG waveforms. It has beenfound that such quasi-sinusoidal seizure onsets respond well to burstsof electrical pulses applied at or near the focus of the activity. Asecond type of seizure onset is defined by sharp, spiky EEG waveforms.Such onsets often do not respond well to bursts of electrical pulses,and alternative therapy approaches (such as relatively low-frequencysinusoidal stimulation) might be more effective.

There are other possible onset types; they may or may not be responsiveto the types of therapy outlined above. For example, different onsettypes might also be defined by the presence or absence of a “beta buzz”(regular rhythmic activity generally in the 13-20 Hz range), whether EEGlevel suppression has occurred, or the presence of specific high- orlow-frequency content in pre-onset electrographic measurements. As willbe shown below, the embodiments described herein are flexible enough tomeasure, identify, and thereafter effectively treat nearly any kind ofcharacteristic or stereotypical brain activity that can be clinicallyobserved in EEG, electrophysiological conditions, or nearly any othermeasurable signal or quantity.

The location of a seizure onset can also provide useful information fora system according to some embodiments. For example, whether a seizureonset occurs in the temporal lobe or extra-temporally might promptdifferent treatment approaches. Also, it may be clinically relevantwhether a detected seizure or its onset has occurred locally (i.e., nearthe detecting electrodes) or remotely (activity somewhere else in thebrain that has propagated). It may be possible in some circumstances todifferentiate local epileptiform and remote propagated activity based onobserved electrographic activity. See, e.g., Y. Schiller et al.,“Characterization and Comparison of Local Onset and Remote PropagatedElectrographic Seizures Recorded with Intracranial Electrodes,”Epilepsia, 39(4): 380-88 (1998) (examining local and remoteelectrographic patterns relating to both mesiotemporal and neocorticalseizure onsets). In particular, rhythmic rounded theta-delta (up toabout 7.5 Hz) waveforms are generally associated with propagatedactivity.

Whether a seizure has generalized might also be important; this canfrequently be determined by comparing electrographic activity observedwith multiple distant sets of detection electrodes (by determiningwhether epileptiform activity is present in multiple parts of thepatient's brain simultaneously), or by considering the characteristicsof the activity itself (as above, with reference to propagatedactivity). Activity that has not yet generalized is treatable viaelectrical stimulation at or near the focus, as such stimulation willtend to disrupt the onset. However, previously generalized (or primarilygeneralized) seizure activity may be more effectively treated byalternative means targeting a functionally relevant portion of thepatient's brain (or even the entire brain), such as responsive drugtherapy or electrical stimulation of a brain structure such as thecaudate nucleus. The caudate nucleus regulates cortical activity, and ithas been found that stimulation of the head of the caudate nucleus canterminate seizures. See S Chkhenkeli et al., “Effects of TherapeuticStimulation of Nucleus Caudatus on Epileptic Electrical Activity ofBrain in Patients with Intractable Epilepsy,” Stereotact. Funct.Neurosurg., 69: 221-224 (1997). Other examples will be set forth below.

Active measurement of electrophysiological conditions is an emerging andpromising factor in identifying and treating seizures and their onsets.See U.S. patent application Ser. No. 09/706,322, filed Nov. 3, 2000,which is hereby incorporated by reference as though set forth in fullherein; it includes a detailed description of possibleelectrophysiological measurement methods advantageously employed in thecontext of the some embodiments. Electrophysiological conditions can beused alone (as in the reference cited above) or in combination withevents detected by other means to guide treatment. For example, whenexcitation or inhibition is found to be abnormal, a certain onsetpattern may be particularly likely to result in a full-blown clinicalseizure, warranting more aggressive treatment than would be ordinarilyattempted in the absence of the electrophysiological condition. Inparticular, trends and historical electrophysiological behavior areexpected to provide particularly valuable information.

Finally, there is a practically limitless number of possible othermeasurements and observations that can be made using various sensors inconnection with a system according to various embodiments, such as fortemperature, blood pressure, sleep or arousal state, cerebral blood flowrate, blood oxygenation, drug concentration, neurotransmitterconcentration, orientation (for detecting rest or sleep), oracceleration or angular velocity (particularly advantageous for use inconnection with movement disorders). Factors observable by any or all ofthese sensors can be used advantageously to drive therapy decisions by asystem according to the various embodiments. Sleep or arousal state, forexample (as determined electrographically, via other sensormeasurements, or inferred from data such as time of day and orientation)may be advantageously used to control the aggressiveness of certaintherapies, as a patient may be more or less likely to suffer a seizure(or other neurological event) when asleep.

System state observations, such as whether programmed or responsivetherapy has been applied recently, whether multiple detections haveoccurred within a short period of time, the elapsed time since adetection or therapy, or the time of day (to name a few simple examples)might also be used to alter therapy delivery according to the someembodiments. Elapsed time, in particular, can be used to guide theaggressiveness of therapy, for example to provide a more sustainedresponse when there has been a relatively long time since the lastevent.

As will be described in greater detail below, all of these possibilitiesare considered to be within the scope of and consistent with variousembodiments described herein.

A neurostimulator 110 according to an embodiment, as it is implantedintracranially, is illustrated in detail in FIG. 1. The neurostimulator110 is affixed in the patient's cranium 112 by way of a ferrule 118. Theferrule 118 is a structural member adapted to fit into a cranialopening, attach to the cranium 112, and retain the neurostimulator 110.

To implant the neurostimulator 110, a craniotomy is performed in theparietal bone anterior to the lambdoidal suture 114 to define an opening120 slightly larger than the neurostimulator 110. The ferrule 118 isinserted into the opening 120 and affixed to the cranium 112, ensuring atight and secure fit. The neurostimulator 110 is then inserted into andaffixed to the ferrule 118.

As shown in FIG. 1, the neurostimulator 110 includes a lead connector122 adapted to receive one or more electrical leads, such as a firstlead 124. The lead connector 122 acts to physically secure the lead 124to the neurostimulator 110, and facilitates electrical connection to aconductor in the lead 124 coupling an electrode to circuitry within theneurostimulator 110. The lead connector 122 accomplishes this in asubstantially fluid-tight environment with biocompatible materials.

The lead 124, as illustrated, and other leads for use in a system ormethod in some embodiments, is a flexible elongated member having one ormore conductors. As shown, the lead 124 is coupled to theneurostimulator 110 via the lead connector 122, and is generallysituated on the outer surface of the cranium 112 (and under thepatient's scalp), extending between the neurostimulator 110 and a burrhole 126 or other cranial opening, where the lead 124 enters the cranium112 and is coupled to at least one depth or cortical electrode implantedin a desired location in or on the patient's brain. If the length of thelead 124 is substantially greater than the distance between theneurostimulator 110 and the burr hole 126, any excess may be urged intoa coil configuration under the scalp. As described in U.S. Pat. No.6,006,124 to Fischell, et al., which is hereby incorporated by referenceas though set forth in full herein, the burr hole 126 is sealed afterimplantation to prevent further movement of the lead 124; in anembodiment, a burr hole cover apparatus is affixed to the cranium 112 atleast partially within the burr hole 126 to provide this functionality.

The neurostimulator 110 includes a durable outer housing 128 fabricatedfrom a biocompatible material. Titanium, which is light, extremelystrong, and biocompatible, is used in analogous devices, such as cardiacpacemakers, and would serve advantageously in this context. As theneurostimulator 110 is self-contained, the housing 128 encloses abattery and any electronic circuitry necessary or desirable to providethe functionality described herein, as well as any other features. Aswill be described further below, a telemetry coil or other antenna maybe provided outside of the housing 128 (and potentially integrated withthe lead connector 122) to facilitate communication between theneurostimulator 110 and external devices.

The neurostimulator configuration described herein and illustrated inFIG. 1 provides several advantages over alternative designs. First, theself-contained nature of the neurostimulator substantially decreases theneed for access to the neurostimulator 110, allowing the patient toparticipate in normal life activities. Its small size and intracranialplacement causes a minimum of cosmetic disfigurement. Theneurostimulator 110 will fit in an opening in the patient's cranium,under the patient's scalp with little noticeable protrusion or bulge.The ferrule 118 used for implantation allows the craniotomy to beperformed and fit verified without the possibility of breaking theneurostimulator 110, and also provides protection against theneurostimulator 110 being pushed into the brain under external pressureor impact. A further advantage is that the ferrule 118 receives anycranial bone growth, so at explant, the neurostimulator 110 can bereplaced without removing any bone screws—only the fasteners retainingthe neurostimulator 110 in the ferrule 118 need be manipulated.

Other implantation configurations and methods of attachment are, ofcourse, possible. In particular, it should be recognized that theneurostimulator 110 can be intracranially attached in other ways thanusing a ferrule, or might be sufficiently thin to be located under thepatient's scalp without the need for a craniotomy. It is also possibleto implant a neurostimulator 110 according to an embodiment in locationsother than the patient's head 116; for example, a pectorally-implantedunit might have relatively longer leads that extend to the desiredlocations in and around the patient's brain.

As stated above, and as illustrated in FIG. 2, a neurostimulatoraccording to an embodiment operates in conjunction with externalequipment. The implantable neurostimulator 110 is mostly autonomous(particularly when performing its usual sensing, detection, andstimulation capabilities), but preferably includes a selectablepart-time wireless link 210 to external equipment such as a programmer212. In an embodiment, the wireless link 210 is established by moving awand (or other apparatus) having communication capabilities and coupledto the programmer 212 into communication range of the implantableneurostimulator 110. The programmer 212 can then be used to manuallycontrol the operation of the device, as well as to transmit informationto or receive information from the implantable neurostimulator 110.Several specific capabilities and operations performed by the programmer212 in conjunction with the device will be described in further detailbelow.

The programmer 212 is capable of performing a number of advantageousoperations in connection with some embodiments. In particular, theprogrammer 212 is able to specify and set variable parameters in theimplantable neurostimulator 110 to adapt the function of the device tomeet the patient's needs, upload or receive data (including but notlimited to stored EEG waveforms, parameters, or logs of actions taken)from the implantable neurostimulator 110 to the programmer 212, downloador transmit program code and other information from the programmer 212to the implantable neurostimulator 110, or command the implantableneurostimulator 110 to perform specific actions or change modes asdesired by a physician operating the programmer 212. To facilitate thesefunctions, the programmer 212 is adapted to receive clinician input 214and provide clinician output 216; data is transmitted between theprogrammer 212 and the implantable neurostimulator 110 over the wirelesslink 210.

The programmer 212 may be used at a location remote from the implantableneurostimulator 110 if the wireless link 210 is enabled to transmit dataover long distances. For example, the wireless link 210 may beestablished by a short-distance first link between the implantableneurostimulator 110 and a transceiver, with the transceiver enabled torelay communications over long distances to a remote programmer 212,either wirelessly (for example, over a wireless computer network) or viaa wired communications link (such as a telephonic circuit or a computernetwork).

The programmer 212 may also be coupled via a communication link 218 to anetwork 220 such as the Internet. This allows any information uploadedfrom the implantable neurostimulator 110, as well as any program code orother information to be downloaded to the implantable neurostimulator110, to be stored in a database 222 at one or more data repositorylocations (which may include various servers and network-connectedprogrammers like the programmer 212). This would allow a patient (andthe patient's physician) to have access to important data, includingpast treatment information and software updates, essentially anywhere inthe world that there is a programmer (like the programmer 212) and anetwork connection. Alternatively, the programmer 212 may be connectedto the database 222 over a trans-telephonic link.

In some embodiments, the wireless link 210 from the implantableneurostimulator 110 may enable a transfer of data from theneurostimulator 110 to the database 222 without any involvement by theprogrammer 212. In these embodiments, the wireless link 210 may beestablished by a short-distance first link between the implantableneurostimulator 110 and a transceiver, with the transceiver enabled torelay communications over long distances to the database 222, eitherwirelessly (for example, over a wireless computer network) or via awired communications link (such as trans-telephonically over atelephonic circuit, or over a computer network).

In some embodiments, the implantable neurostimulator 110 is also adaptedto receive communications from an initiating device 224, typicallycontrolled by the patient or a caregiver. Accordingly, patient input 226from the initiating device 224 is transmitted over a wireless link tothe implantable neurostimulator 110; such patient input 226 may be usedto cause the implantable neurostimulator 110 to switch modes (on to offand vice versa, for example) or perform an action (e.g., store a recordof EEG data). Preferably, the initiating device 224 is able tocommunicate with the implantable neurostimulator 110 through thecommunication subsystem 130 (FIG. 1), and possibly in the same mannerthe programmer 212 does. The link may be unidirectional (as with themagnet and GMR sensor described above), allowing commands to be passedin a, single direction from the initiating device 224 to the implantableneurostimulator 110, but in some embodiments is bi-directional, allowingstatus and data to be passed back to the initiating device 224.Accordingly, the initiating device 224 may be a programmable PDA orother hand-held computing device, such as a Palm Pilot®. or PocketPC®.However, a simple form of initiating device 224 may take the form of apermanent magnet, if the communication subsystem 130 is adapted toidentify magnetic fields and interruptions therein as communicationsignals.

In some embodiments, the programmer 212 is primarily a commerciallyavailable PC, laptop computer, or workstation having a CPU, keyboard,mouse and display, and running a standard operating system such asMicrosoft Windows®, Linux®, Unix®, or Apple Mac OS®. It is alsoenvisioned that a dedicated programmer apparatus with a custom softwarepackage (which may not use a standard operating system) could bedeveloped.

When running the computer workstation software operating program, theprogrammer 212 can process, store, play back and display on the displaythe patient's EEG signals, as previously stored by the implantableneurostimulator 110 of the implantable neurostimulator device.

The computer workstation software operating program also has thecapability to simulate the detection and prediction of sensor signalactivity representative of movement disorders, such as the tremordescribed herein. Included in that capability, the software operatingprogram may have the capability to allow a clinician to create or modifya patient-specific collection of information comprising, in oneembodiment, algorithms and algorithm parameters for the detection ofrelevant sensor signal activity. The patient-specific collection ofdetection algorithms and parameters used for neurological activitydetection in some embodiments will be referred to herein as a detectiontemplate or patient-specific template. The patient-specific template, inconjunction with other information and parameters generally transferredfrom the programmer to the implanted device (such as stimulationparameters, time schedules, and other patient-specific information),make up a set of operational parameters for the neurostimulator.

Following the development of a patient specific template on theworkstation 212, the patient-specific template would be downloadedthrough the communications link 210 from the programmer 212 to theimplantable neurostimulator 110.

The patient-specific template is used by the detection subsystem 122 andthe CPU 128 of the implantable neurostimulator 110 to detect activityrepresentative of a symptom of a movement disorder in the patient's EEGsignals (or other sensor signals), which can be programmed by aclinician to result in responsive stimulation of the patient's brain, aswell as the storage of EEG records before and after the detection,facilitating later clinician review.

In some embodiments, the database 222 is adapted to communicate over thenetwork 220 with multiple programmers, including the programmer 212 andadditional programmers 228, 230, and 232. It is contemplated thatprogrammers will be located at various medical facilities andphysicians' offices at widely distributed locations. Accordingly, ifmore than one programmer has been used to upload EEG records from apatient's implantable neurostimulator 110, the EEG records will beaggregated via the database 222 and available thereafter to any of theprogrammers connected to the network 220, including the programmer 212.

An overall block diagram of the neurostimulator 110 used formeasurement, detection, and treatment in some embodiments is illustratedin FIG. 3. Inside the housing 128 (FIG. 1) of the neurostimulator 110are several subsystems making up a control module 310. The controlmodule 310 is capable of being coupled to a plurality of electrodes 312,314, 316, and 318 (each of which may be connected to the control module310 via a lead for sensing, stimulation, or both. In the illustratedembodiment, the coupling is accomplished through the lead connector 122(FIG. 1). Although four electrodes are shown in FIG. 3, it should berecognized that any number is possible, and in the embodiment describedin detail below, eight electrodes are used. In fact, it is possible toemploy an embodiment that uses a single lead with at least twoelectrodes, or two leads each with a single electrode (or with a secondelectrode provided by a conductive exterior portion of the housing 128in one embodiment), although bipolar sensing between two closely spacedelectrodes on a lead is preferred to minimize common mode signalsincluding noise.

The electrodes 312-318 are connected to an electrode interface 320. Insome embodiments, the electrode interface is capable of selecting eachelectrode as required for sensing and stimulation. The electrodeinterface 320 also may provide any other features, capabilities, oraspects, including but not limited to amplification, isolation, andcharge-balancing functions, that are required for a proper interfacewith neurological tissue and not provided by any other subsystem of theneurostimulator 110. The electrode interface 320, an external sensor322, and an internal sensor 324 are all coupled to a detection subsystem326; the electrode interface 320 is also connected to a therapysubsystem 328.

The detection subsystem 326 includes an EEG analyzer function. The EEGanalyzer function, which will be described in greater detail below, isadapted to receive EEG and other signals from the electrodes 312-318,through the electrode interface 320, and to process those signals toidentify neurological activity indicative of a seizure, a seizure onset,or any other neurological activity of interest; various inventivemethods for performing such detection are described in detail below.

The detection subsystem may optionally also contain further sensing anddetection capabilities, including but not limited to parameters derivedfrom other physiological conditions (such as electrophysiologicalparameters, temperature, blood pressure, etc.), which may be sensed bythe external sensor 322 or the internal sensor 324. These conditionswill be discussed in additional detail below. In particular, it may beadvantageous to provide an accelerometer, an angular velocity sensor, oran EMG sensing electrode as the external sensor at a location remotefrom the implantable neurostimulator 110 (e.g., in the case of amovement disorder, in one of the patient's limbs that is subject totremor). The external sensor 322 can be connected to the neurostimulator110 (and the detection subsystem 326) by a lead or by wirelesscommunication, such as a wireless intrabody signaling technique. Todetect head tremor, a clinical seizure, or orientation (e.g., for sleepdetection), an accelerometer might be used as the internal sensor 324.Other sensors, such as for temperature, blood pressure, bloodoxygenation, drug concentration, or neurotransmitter concentration mightbe implemented as part of the external sensor 322 or the internal sensor324. Other sensor configurations are of course possible and areconsidered to be usable in various embodiments.

The therapy subsystem 328 is primarily capable of applying electricalstimulation to neurological tissue through the electrodes 312-318. Thiscan be accomplished in any of a number of different manners. Forexample, it may be advantageous in some circumstances to providestimulation in the form of a substantially continuous stream of pulses,or on a scheduled basis. This form of stimulation, referred to herein asprogrammed stimulation, is provided by a programmed stimulation function332 of the therapy subsystem 328. Preferably, therapeutic stimulation isalso provided in, response to abnormal events detected by the dataanalysis functions of the detection subsystem 326. This form ofstimulation, namely responsive stimulation, is provided by a responsivestimulation function 330 of the therapy subsystem 328.

As illustrated in FIG. 3, the therapy subsystem 328 and the dataanalysis functions of the detection subsystem 326 are in communication;this facilitates the ability of therapy subsystem 328 to provideresponsive stimulation as well as an ability of the detection subsystem326 to blank the amplifiers while stimulation is being performed tominimize stimulation artifacts. It is contemplated that the parametersof the stimulation signal (e.g., frequency, duration, waveform) providedby the therapy subsystem 328 would be specified by other subsystems inthe control module 310, as will be described in further detail below.

In some embodiments, the therapy subsystem 328 is also capable of a drugtherapy function 334, in which a drug is dispensed from a drug dispenser336 (which may be integral with the control module 310 or an externalunit). As with electrical stimulation, this capability can be providedeither on a programmed basis (or continuously) or responsively, after anevent of some kind is detected by the detection subsystem 326.

Also in the control module 310 is a memory subsystem 338 and a centralprocessing unit (CPU) 340, which can take the form of a microcontroller.The memory subsystem 338 is coupled to the detection subsystem 326(e.g., for receiving and storing data representative of sensed EEGsignals and other sensor data), the therapy subsystem 328 (e.g., forproviding stimulation waveform parameters to the stimulation subsystem),and the CPU 340, which can control the operation of the memory subsystem338. In addition to the memory subsystem 338, the CPU 340 is alsoconnected to the detection subsystem 326 and the therapy subsystem 328for direct control of those subsystems.

Also provided in the control module 310, and coupled to the memorysubsystem 338 and the CPU 340, is a communication subsystem 342. Thecommunication subsystem 434 enables communication between theimplantable neurostimulator 110 (FIG. 1) and the outside world,particularly the external programmer 212 (FIG. 2). As set forth above,in some embodiments, the communication subsystem 342 includes atelemetry coil (which may be situated outside of the housing 128)enabling transmission and reception of signals, to or from an externalapparatus, via inductive coupling. Alternative embodiments of thecommunication subsystem 342 could use an antenna for an RF link or anaudio transducer for an audio link (which, as described below, can alsoserve as an audio warning transducer).

Rounding out the subsystems in the control module 310 are a power supply344 and a clock supply 346. The power supply 344 supplies the voltagesand currents necessary for each of the other subsystems. The clocksupply 346 supplies substantially all of the other subsystems with anyclock and timing signals necessary for their operation.

It should be observed that while the memory subsystem 338 is illustratedin FIG. 3 as a separate functional subsystem, the other subsystems mayalso require various amounts of memory to perform the functionsdescribed above and others. Furthermore, while the control module 310 ispreferably a single physical unit contained within a single physicalenclosure, namely the housing 128 (FIG. 1), it may comprise a pluralityof spatially separate units each performing a subset of the capabilitiesdescribed above. Also, it should be noted that the various functions andcapabilities of the subsystems described above may be performed byelectronic hardware, computer software (or firmware), or a combinationthereof. The division of work between the CPU 340 and the otherfunctional subsystems may also vary—the functional distinctionsillustrated in FIG. 3 may not reflect the integration of functions in areal-world system or method in some embodiments.

The implantable neurostimulator 110 (FIG. 1) generally interacts withthe programmer 212 (FIG. 2) as described below. Data stored in thememory subsystem 338 can be retrieved by the patient's physician throughthe wireless communication link 210, which operates through thecommunication subsystem 342 of the implantable neurostimulator 110. Inconnection with some embodiments, a software operating program run bythe programmer 212 allows the physician to read out a history of eventsdetected including EEG information before, during, and after each event,as well as specific information relating to the detection of each event(such as, in one embodiment, the time-evolving energy spectrum of thepatient's EEG). The programmer 212 also allows the physician to specifyor alter any programmable parameters of the implantable neurostimulator110. The software operating program also includes tools for the analysisand processing of recorded EEG records to assist the physician indeveloping optimized tremor detection parameters for each specificpatient, and to identify which therapies in conjunction with someembodiments are most advantageously associated with what eventcharacteristics.

FIG. 4 illustrates details of the detection subsystem 326 (FIG. 3).Inputs from the electrodes 312-318 are on the left, and connections toother subsystems are on the right.

Signals received from the electrodes 312-318 (as routed through theelectrode interface 320) are received in an electrode selector 410. Theelectrode selector 410 allows the device to select which electrodes (ofthe electrodes 312-318) should be routed to which individual sensingchannels of the detection subsystem 326, based on commands receivedthrough a control interface 426 from the memory subsystem 338 or the CPU340 (FIG. 3). Preferably, each sensing channel of the detectionsubsystem 326 receives a bipolar signal representative of the differencein electrical potential between two selectable electrodes.

Accordingly, the electrode selector 410 provides signals correspondingto each pair of selected electrodes (of the electrodes 312-318) to asensing front end 412, which performs amplification, analog to digitalconversion, and multiplexing functions on the signals in the sensingchannels. Preferably, any of the electrodes 312-318 can be unused (i.e.,not connected to any sensing channel), coupled to a positive or negativeinput of a single sensing channel, coupled to the positive inputs ofmultiple sensing channels, or coupled to the negative inputs of multiplesensing channels.

A multiplexed input signal representative of all active sensing channelsis then fed from the sensing front end 412 to a data analyzer 414. Thedata analyzer 414 is preferably a special-purpose digital signalprocessor (DSP) adapted for use in some embodiments, or in somealternative embodiments, may comprise a programmable general-purposeDSP.

In some embodiments, the data analyzer 414 is capable of performingthree functions, namely, an EEG waveform analysis function 418, anelectrophysiological waveform analysis function 420, and a sensor signalanalysis function 422. It will be recognized that some or all of thesefunctions can be performed with the same software or hardware in thedata analyzer 414, by simply operating with different parameters ondifferent types of input data. It is also possible, of course, tocombine the three functions in many ways to detect neurological eventsor conditions, or to identify event characteristics in connection withsome embodiments.

In some embodiments, the data analyzer has its own scratchpad memoryarea 424 used for local storage of data and program variables when thesignal processing is being performed.

In either case, the signal processor performs suitable measurement anddetection methods described generally above and in greater detail below.

As described in U.S. patent application Ser. No. 09/896,092, filed onJun. 28, 2001, which is hereby incorporated by reference as though setforth in full herein, a responsive neurostimulator in some embodimentsis capable of using three different kinds of analysis tools in variouscombinations, namely a half wave analysis tool, a line length analysistool, and an area analysis tool. There are preferably multiple instancesof each analysis tool, each of which can be set up with differentdetection parameters and coupled to a different input sensing channel ifdesired.

The half wave analysis tool measures characteristics of an EEG signalrelated to the signal's dominant frequency content. In general terms, ahalf wave is an interval between a local waveform minimum and a localwaveform maximum; each time a signal “changes directions” (fromincreasing to decreasing, or vice versa), subject to limitations thatwill be set forth in further detail below, a new half wave isidentified.

The identification of half waves having specific amplitude and durationcriteria allows some frequency-driven characteristics of the EEG signalto be considered and analyzed without the need for computationallyintensive transformations of normally time-domain EEG signals into thefrequency domain. Specifically, the half wave feature extractioncapability identifies those half waves in the input signal having aduration that exceeds a minimum duration criterion and an amplitude thatexceeds a minimum amplitude criterion. The number of half waves in atime window meeting those criteria is somewhat representative of theamount of energy in a waveform at a frequency below the frequencycorresponding to the minimum duration criterion. And the number of halfwaves in a time window is constrained somewhat by the duration of eachhalf wave (i.e., if the half waves in a time window have particularlylong durations, relatively fewer of them will fit into the time window),that number is highest when a dominant waveform frequency most closelymatches the frequency corresponding to the minimum duration criterion.

Accordingly, the number of qualified half waves (i.e., half wavesmeeting both the duration criterion and the amplitude criterion) withina limited time period is a quantity of interest, as it may berepresentative of neurological events manifested in the specifiedfrequency range corresponding to the half wave criteria. The half waveanalysis tool, particularly when used on filtered EEG data, can be usedto identify the presence of signals in a particular desired frequencyrange.

The line length analysis tool is a simplification of waveform fractaldimension, allowing a consideration of how much variation an EEG signalundergoes. Accordingly, the line length analysis tool in someembodiments enables the calculation of a “line length” for an EEG signalwithin a time window. Specifically, the line length of a digital signalrepresents an accumulation of the sample-to-sample amplitude, variationin the EEG signal within a time window. Stated another way, the linelength is representative of the variability of the input signal. Aconstant input signal will have a line length approaching zero(representative of substantially no variation in the signal amplitude),while an input signal that oscillates between extrema from sample tosample will approach the maximum line length. It should be noted thatwhile “line length” has a mathematical-world analogue in measuring thevector distance travelled in a graph of the input signal, the concept ofline length as treated herein disregards the horizontal (X) axis in sucha situation. The horizontal axis herein is representative of time, whichis not combinable in any meaningful way in some embodiments withinformation relating to the vertical (Y) axis, generally representativeof amplitude, and which in any event would contribute nothing ofinterest.

The area analysis tool is a simplification of waveform energy.Accordingly, the area analysis tool in some embodiments enables thecalculation of the area under the EEG waveform curve within a timewindow. Specifically, the area function is calculated as an aggregationof the EEG's signal total deviation from zero over the time window,whether positive or negative. The mathematical-world analogue for thearea function is the mathematical integral of the absolute value of theEEG function (as both positive and negative signals contribute topositive energy). Once again, the horizontal axis (time) makes nocontribution to the area under the curve as treated herein. Accordingly,an input signal that remains around zero will have a small area, whilean input signal that remains around the most-positive or most-negativevalues (or oscillates between those values) will have a high area.

Any of the three detection tools summarized above (and described indetail in U.S. patent application Ser. No. 09/896,092, filed on Jun. 28,2001) can be used in connection with any of the three functions of thedata analyzer 414, and can be easily tuned to operate on essentially anykind of source data.

In some embodiments, the data analyzer 414 is adapted to deriveparameters from an input signal not only for detection purposes, butalso to achieve the desired stimulation timing in some embodiments. Itis useful for a data analyzer 414 in some embodiments to have multiplemappable channels, allowing at least a single channel to be configuredspecifically to derive signal timing for adaptive stimulation signalsynchronization, and other channels to be used for event detection. SeeU.S. patent application Ser. No. 09/896,092, referenced above, fordetails on a multi-channel detection subsystem programmable as describedherein.

The half wave analysis tool is particularly useful for providingadaptive stimulation parameters in some embodiments, as qualified halfwaves derived as set forth above are discrete and identifiable featuresof an electrographic waveform that, have well-defined amplitudes,durations, and start and end times that are advantageously mappable tostimulation signal characteristics.

There are multiple instances and channels of half wave analysis tools,as described above, and the multiple instances can analyze separateinput channels with different signal processing and detectionparameters. It should be noted that this capability is particularlyadvantageous in some embodiments, as certain signal processing and halfwave detection parameters may be used for neurological event detectionand others used for synchronization and adaptive stimulation asdescribed herein. In particular, certain qualified half waves, namelythose signal half waves meeting minimum amplitude and minimum durationcriteria useful for event detection, may not be best suited forstimulation timing. Therefore, in some embodiments, one instance of thehalf wave analysis tool is dedicated to deriving qualified half wavesspecifically for use as synchronization points for adaptive stimulation,as will be described in further detail below. This half wave analysistool can receive either the same signal that is used for detection or adifferent signal, depending on how the neurostimulator device 110 isprogrammed and configured.

Any results from the detection methods described above, as well as anydigitized signals intended for storage and subsequent transmission toexternal equipment, are passed to various other subsystems of thecontrol module 310, including the memory subsystem 338 and the CPU 340(FIG. 3) through a data interface 428. Similarly, the control interface426 allows the data analyzer 414 and the electrode selector 410 to be incommunication with the CPU 340.

Again, the functional distinctions illustrated in FIG. 4, which arepresented as separate functions for clarity and understandabilityherein, might not be meaningful distinctions in some embodiments.

The various functions and capabilities of the therapy subsystem 328(FIG. 3) are illustrated in greater detail in FIG. 5. Consistent withFIG. 4, inputs to the therapy subsystem 328 are shown on the right, andoutputs are on the left.

Referring initially to the input side of FIG. 5, the stimulationsubsystem 328 includes a control interface 510, which receives commands,data, and other information from the CPU 340, the memory subsystem 338,and the detection subsystem 326 (FIG. 3). The control interface 510 usesthe received commands, data, and other information to control atherapeutic stimulator 512, a sensory stimulator 514, and a diagnosticstimulator 516. The therapeutic stimulator 512 is adapted to provideelectrical stimulation signals appropriate for application toneurological tissue to terminate a present or predicted undesiredneurological event, especially an epileptic seizure (or its precursor).As set forth above, the therapeutic stimulator 512 is typicallyactivated in response to conditions detected by the sensing subsystem522, but may also provide some substantially continuous or programmed orscheduled stimulation. The sensory stimulator 514 is also typicallyactivated in response to a detection by the sensing subsystem; it mayelectrically stimulate enervated tissue (such as the scalp) to provide atactile sensation to the patient, or may alternatively include an audioor visual transducer to provide audiovisual cues (such as warnings) tothe patient.

The diagnostic stimulator 516, which is used to perform activeelectrophysiological diagnostic measurements in connection with someembodiments, includes two sub-functions, an excitability stimulator 518and a refractoriness stimulator 520, though both functions may beperformed by the same circuit under differing controls from the controlinterface 510. The excitability stimulator 518 and the refractorinessstimulator 520 both act under the control of the detection subsystem 326to provide the stimulation signals used for the effective measurement ofelectrophysiological parameters in some embodiments. In one embodiment,the excitability stimulator 518 provides pulses at varying currentlevels to test the excitability of neural tissue, while therefractoriness stimulator 520 provides pairs of pulses with varyinginter-pulse intervals to test the inhibitory characteristics of neuraltissue. For details on how active electrophysiological diagnostics areperformed as used herein, see U.S. patent application Ser. No.09/706,322, filed on Nov. 3, 2000, which is hereby incorporated byreference as though set forth in full herein.

The therapy subsystem 328 also includes a drug dispenser controller 522,which under the control of the control interface 510 (and the memorysubsystem 338, the CPU 340, and the detection subsystem 326), is adaptedto selectively allow the release of a drug or other therapeutic agentfrom a drug dispenser 336 (which typically contains a reservoir) to oneor more desired sites, within or near the patient's brain or elsewherein the body. As with therapeutic stimulation described above, drugtherapy can be performed on a responsive basis (i.e., in response to adetected neurological event or condition), on a substantially continuousbasis, or as programmed or scheduled.

The therapeutic stimulator 512, the sensory stimulator 514, and thediagnostic stimulator 516 are all coupled to a multiplexer 524, which iscontrollable to select the appropriate types of stimulation and passthem along to a stimulation signal generator 526. The multiplexer 524may allow only one type of stimulation to be performed at a time, but insome embodiments, the multiplexer 524 allows different types ofstimulation to be selectively applied to the different electrodes312-318, either sequentially or substantially simultaneously. Thestimulation signal generator 526 receives commands and data from thetherapeutic stimulator 512, the sensory stimulator 514, and thediagnostic stimulator 516, and generates electrical stimulation signalshaving the desired characteristics that are properly time-correlated andassociated with the correct electrodes, and receives power from acontrollable voltage multiplier 528 to facilitate the application of aproper voltage and current to the desired neurological tissue. Thevoltage multiplier 528 is capable of creating relatively high voltagesfrom a battery power source, which typically has a very low voltage;circuits to accomplish this function are well known in the art ofelectronics design. The stimulation signal generator 526 has a pluralityof outputs, which in the disclosed embodiment are coupled to theelectrode interface 320 (FIG. 3). In various embodiments, thestimulation signal generator 526 can perform signal isolation,multiplexing, and queuing functions if the electrode interface 320 doesnot perform such functions.

It should be recognized that while various functional blocks areillustrated in FIG. 5, not all of them might be present in an operativeembodiment. Furthermore, as with the overall block diagram of FIG. 3,the functional distinctions illustrated in FIG. 5, which are presentedas separate functions for clarity and understandability herein, mightnot be meaningful distinctions in some embodiments. For example, in thepresently preferred embodiment, the various stimulation types (providedin FIG. 5 by stimulators 512-516) are all accomplished with a singlecircuit selectively controlled with different parameters; there is asingle controllable stimulator capable of selectively providing signalsfor therapeutic stimulation, diagnostic stimulation, and sensorystimulation.

Referring now to FIG. 6, a first modality of treatment, bursts ofbiphasic pulses, is illustrated by a first stimulation waveform 610.This type of stimulation has been found to be advantageously applied ator near a seizure focus upon detection of an onset to prevent a clinicalseizure from occurring. It is also usable for programmed stimulation, atvarious amplitudes, to reduce susceptibility to undesired activity, andfor acute stimulation at functionally relevant brain structures.

A second modality of treatment is illustrated by a second stimulationwaveform 612, which generally represents a stepwise approximation of asinusoidal signal. Such a signal can be applied to terminate certainkinds of epileptiform activity, as described above, or also potentiallyas a continuous, semi-continuous, or programmed sub-thresholdstimulation to reduce susceptibility to seizures or other undesiredactivity. Although the second stimulation waveform 612 is illustrated asa digitally-generated approximation of a sinusoidal waveform, it shouldbe recognized that waveforms more closely resembling sine waves (andtrue sine waves) might be applied instead; the stepwise approximation isadvantageously used to leverage existing waveform playback anddigital-to-analog conversion capabilities of a system according to someembodiments. Haversine and other smoothed signals might also be used tosimilar effect, with or without DC offset.

Finally, a third modality of stimulation therapy is illustrated inconnection with an exemplary electrographic waveform 614, which isrelated to a stimulation pulse specially timed according to someembodiments. The electrographic waveform 614, which is of the generaltype that would be received and processed by the implantableneurostimulator 110 (via the electrodes 312-318, passed through theelectrode interface 320 to the detection subsystem 326), has a seizureportion 616 that clearly visually represents rhythmic epileptiformactivity. The specific characteristics of the waveform 614 are exemplaryonly and for purposes of illustration; they are not necessarily intendedto reflect a possible real-world scenario. It should be noted inparticular that although the seizure portion 616 of the electrographicwaveform 614 is clearly apparent in FIG. 6, that would not necessarilybe the case in an actual implementation of a system in some embodiments.

A small segment 618 of the seizure portion 616 is magnified and shown asa magnified segment 620. The magnified segment 620 will be used toillustrate the derivation of waveform characteristics of interest andthe delivery of an adaptive stimulation signal according to someembodiments. As illustrated, an increasing half wave 622 represents asubstantially monotonic (exclusive of a small hysteresis allowance)increasing portion of the magnified segment 620 between a local minimum624 and a local maximum 626 of the waveform 614. The amplitudedifference (on the Y axis) between the local minimum 624 and the localmaximum 626 is the amplitude 628 of the half wave, and the timedifference (on the X axis) between the local minimum 624 and the localmaximum 626 is the duration 630 of the half wave. If the amplitude 628and duration 630 exceed respective thresholds, then the observed halfwave is considered a “qualified half wave,” and is generally regarded asrepresentative of the dominant frequency and amplitude of theelectrographic waveform. If the observed half wave does not meet thethresholds, it is disregarded. For details on half wave measurement,see, e.g., U.S. patent application Ser. No. 09/896,092, referencedabove. It should be noted that even if a qualified half wave meetsminimum amplitude and duration thresholds, it is not necessarily trulyrepresentative of the underlying signal's frequency or wavelength; it isonly a single measurement from what is likely a complex waveform.

As will be described in further detail below, once an event detectionhas been made, the amplitude 628 and duration 630 are used in variousways by a system according to some embodiments to synchronize ordesynchronize a stimulation signal to the waveform 614.

As illustrated in FIG. 6, in an embodiment, a biphasic stimulation pulse632 is applied after a time delay 634 equal in length to the duration630, thereby approximately synchronizing the pulse 632 to an expectedtrough 636 in the waveform 614. It should be recognized, of course, thatthe duration of a qualified half wave is not necessarily accuratelyrepresentative of the wavelength of the electrographic waveform 614 inthe seizure portion 616 (because of variations in the waveform 614 andin the individual half waves making up the waveform 614), so in practiceit is unlikely that the pulse 632 will be accurately synchronized to thetrough 636. However, after a delay of only one additional half waveduration 630, it is expected that the pulse 632 and the trough 636 maybe relatively close.

After a delay of multiple half wave durations, or after significantprocessing latency, by the neurostimulator 110 synchronization is lesslikely and decorrelation will generally be the primary outcome.Accordingly, if the time delay 634 is set to be a multiple (or someother mathematical transform) of the duration 630, or if there is asignificant amount of latency between measurement of half wave amplitude628 and duration 630 and when a stimulation pulse 632 is applied, thedelay 634 will generally desynchronize stimulation from the waveform 614as a result of accumulated error and changes in the characteristics ofthe waveform 614. As described above, in some embodiments, this maydesirably serve as a variable factor in stimulation to decrease thelikelihood of undesired learning of stimulation characteristics.

In an alternative embodiment, if desired, a pulse amplitude 638 can becorrelated to the half wave amplitude 628 in a similar manner, or bothamplitude 628 and duration 630 can be mapped onto a stimulation pulse.

It should be noted that while a single biphasic pulse 632 is illustratedin FIG. 6, that pulse is not necessarily to scale and is intended onlyto illustrate an exemplary timing relationship between the magnifiedsegment 620 and the start of the pulse 632. The amplitude of the pulse632 may not have the illustrated relationship to the waveform 614. Andin an alternative embodiment, the pulse 632 may have a waveform otherthan a short biphasic pulse, or may be the first portion of a regular orirregular burst of pulses or other signals.

In connection with some embodiments, waveform parameters and othercharacteristics of an event can be used for at least two purposes:first, identifying the nature of the event and selecting the mosteffective therapy given the nature of the event; and second,correlating, decorrelating, or otherwise varying the therapy based on anobserved parameter to provide enhanced therapy, as generally describedin U.S. patent application Ser. No. 09/962,940, of which thisapplication is a continuation-in-part.

A method for applying differential therapy in some embodiments based inpart on a “device context” is illustrated in FIG. 7. Device context, asthe term is used herein, is some measurable or observable aspect,function, or parameter of the neurostimulator 110 that can be used toselect a suitable therapy. One example of device context is whichdetection channel, of multiple detection channels, triggered an eventdetection by the neurostimulator 110.

Initially, a neurological event of interest is detected (step 710); thisneurological event can be a seizure, a seizure onset, an episode of amovement disorder, an episode of pain, or any of numerous otherpossibilities. Once the event is detected, the context is identified(step 712). As described above, one possibility is which detectionchannel was triggered; other possibilities include time of day, the timesince the last detection, the time since the last therapy delivery,physiological or system conditions, or numerous others.

Based on the context, which as observed by the neurostimulator 110 isgenerally a numeric quantity (e.g. elapsed time) or transformable into anumeric quantity (e.g. which detection channel), a therapy is selected(step 714) from a plurality of possible therapies. In some embodiments,the therapy most likely to treat the detected event most effectively (asdetermined by prior clinical testing, either patient-specific orgenerally) is associated with each possible numeric quantity orapplicable ranges of quantities. In a relatively complex embodiment, thepossible therapies include responsive electrical stimulation, initiationof a course of scheduled or programmed electrical stimulation, therelease of a quantity of a drug or other therapeutic agent, or thedelivery of a warning to the patient or another individual. There areother possibilities, and variations within those categories (such as thedelivery of responsive electrical stimulation to various targets) thatshould be considered.

If desired, the selected therapy is then modified or otherwisetransformed (step 716) based on the previously-identified context or anyother value of interest. For example, if a burst of biphasic pulses isselected as the therapy, the frequency or amplitude, or duration of theburst can be modified in some embodiments. Therapy delivery is thenscheduled, and therapy is applied by the neurostimulator 110 asspecified (step 718). If the planned therapy delivery is incomplete(step 720), then additional context measurements can be performed(optionally), and therapy selection, modification, and application arerepeated as necessary (steps 712-718).

As described above, device context can be used to differentiate betweendifferent types and locations of seizure onsets in some embodiments. Ifthe neurostimulator 110 includes multiple active detection channels,each receiving a signal from a different portion of the patient's brain,then the identity of the triggering detection channel is directlyrelated to the location of the detected event, and may also be relatedto the type of the detected event.

Accordingly, using device context according to the method set forth inFIG. 7 is consistent with one of the objectives of some embodiments,namely to treat different types and locations of events differently.Onset type and location may frequently be interrelated, as well; apatient may have one seizure (or other event) type that originatesexclusively in a first location, while a second event type originatesonly elsewhere.

Other forms of device context (e.g., the elapsed time since the mostrecent event detection) also tend to be relevant, as different types ofneurological events tend to be preceded by different kinds of activity.

In relation to the objectives of a system according to some embodiments,it should be observed that possible desired outcomes (depending on thetriggering event) include avoiding or terminating an onset (if thedetected event is a seizure or other event's onset), avoiding orterminating the result of the event (for example, if the event is aseizure onset or the seizure itself), halting the propagation ofundesired activity (for example, if the detected event is a generalizingseizure), reducing the susceptibility of the patient to undesiredactivity (if the detected event is, for example, representative of aprediction or an increased likelihood of a seizure or other problem—suchas interictal spiking), or delivering a warning (in any or all of theforegoing scenarios). Different therapy strategies may be applicable foreach of these scenarios, and the neurostimulator 110 is preferablyprogrammed to select the most effective course.

As recognized above, many different therapy types and subtypes arepossible in various embodiments. Several permutations may beillustrative: responsive, continuous, or programmed electricalstimulation can be applied at or near the event's focus (with one ormore of the following characteristics: pulses, sinusoidal waveforms,sub-threshold stimulation, DC stimulation, adaptively timing);responsive, continuous, or programmed electrical stimulation can beapplied at or near the location where the activity was first detected(with one or more of the foregoing characteristics); responsive,continuous, or programmed electrical stimulation can be applied at afunctionally relevant brain area (with one or more of the same possiblecharacteristics), such as the caudate nucleus, the subthalamic nucleus,the anterior thalamus, the ventralateral thalamus, the globus pallidusinternus, the globus pallidus externus, the substantia nigra, or theneostriatum (or any selected portion of any of these structures);responsive, continuous, or programmed electrical stimulation can beapplied at a peripheral nerve, such as the vagus nerve, or any otherdesired location; drug therapy can be applied to any desired location(in the brain or bloodstream, for example); somatosensory stimulation orsensory stimulation (such as an audio signal) can be provided to thepatient; or a message can be transmitted from the neurostimulator 110 toexternal equipment.

There are many other possibilities and permutations; they will not bedescribed in detail herein, but would be apparent to a practitioner ofordinary skill. Two or more of these therapy types and subtypes can, ofcourse, be combined into a single course of therapy, should it beclinically advantageous to do so.

The method illustrated by the flow chart of FIG. 8 is analogous to themethod of FIG. 7, but uses measurements and other parameters obtained bythe neurostimulator 110, rather than device context, to drive therapyselection.

Initially, a neurological event of interest is detected (step 810); thisneurological event can be a seizure, a seizure onset, an episode of amovement disorder, an episode of pain, or any of numerous otherpossibilities. Once the event is detected, a parameter relating to acharacteristic of the detected event is obtained (step 812).

One advantageously utilized type of parameter is represented by datastored by the neurostimulator 110 in the course of its ordinarymeasurement and detection tasks, such as data related to EEG morphology.For example, to the extent the detection channels of the neurostimulator110 store relatively unprocessed data (for example, half wave, linelength, and area information) upon which detection decisions are made,this information may be advantageously used to derive a characteristicfor any detected event. For example, after an event is detected,retrospective or prospective consideration of half wave densities,signal frequency content or variability, or other characteristics mayprovide useful information as to the nature of the detected event.

Other parameters include measurements performed by the neurostimulator110, such as from the physical and physiological state sensors describedabove (temperature, blood pressure, orientation, etc.), and activeelectrophysiological measurements performed as described above and inconnection with U.S. patent application Ser. No. 09/706,322, referencedabove.

Details of some of these measurement techniques will be set forth inadditional detail below, in connection with FIGS. 9-11.

It should be noted that not only measured parameters themselves, buttrends and historical patterns in such parameters may also be indicativeof a characteristic of the detected neurological event, and variousembodiments are advantageously capable of obtaining, analyzing, andconsidering such trends and historical data as well.

After the parameter (or relevant trend or historical pattern) isobtained, the parameter is transformed (step 814) as desired, typicallyto map the parameter into a desired range or distribution of values.Based on the transformed parameter, then, a therapy is selected (step816) from a plurality of possible therapies. As with the method of FIG.7, above, the therapy most likely to treat the detected event mosteffectively is associated with each possible numeric parameter value orsub-range of values.

If desired, the selected therapy is then modified or otherwisetransformed (step 818) based on the previously-measured parameter or anyother value of interest. Therapy delivery is then scheduled, and therapyis applied by the neurostimulator 110 as specified (step 820). If theplanned therapy delivery is incomplete (step 822), then additionalmeasurements can be optionally performed, and the parametertransformation, therapy selection, modification, and application arerepeated as necessary (steps 812-820).

It should be noted that it is, of course, possible to combine theapproaches of FIG. 7 and FIG. 8 in a single treatment strategy. Forexample, a device context and a measured parameter (obtained in any waydescribed above) can be combined into a single factor to select a courseof therapy, or can be used individually to select and modify one or moretherapy deliveries. Other possible combinations will be apparent.

A particularly effective use of the technology described herein (and themethods set forth in FIGS. 7-8, described above) is in relation topredicted events, namely to provide prophylactic therapy well in advanceof any seizure onset or other clinically undesired event. In particularwhen the detection subsystem 326 (FIG. 3) is configured to detect aprecursor to an event, or some other predictive circumstance thatsuggests or is representative of an increased probability ofencountering the event, it may be advantageous to deliver a course ofresponsive therapy that is best tailored to avoid the event. Inparticular, it may be appropriate to consider the elapsed time since thelast detection or therapy delivery to determine the aggressiveness ofthe response—if it has been a long time since the last event or therapy,or if physiological conditions dictate, it may be best to deliver aparticularly strong and sustained response.

Where a parameter is to be measured from a queue or other storageassociated with a detection channel (or elsewhere in the neurostimulator110), one method for identifying that information is illustrated in FIG.9.

Initially, a detection context is identified (step 910). As with thedevice context described above with reference to FIG. 7, the detectioncontext is some observable aspect, function, or parameter of theneurostimulator 110 that relates to the detection. In some embodiments,the detection context comprises the detection channel that caused anevent detection to take place (see step 810, FIG. 8). The context isthen used to identify which channel it is desired to measure theevent-related parameter from (step 912). In many circumstances, it maybe desirable to observe and measure the parameter from the same channelthat caused the detection (because that channel most like containsmeasurement data most closely related to the observed and detectedevent), but other channels, such as spatially adjacent channels orremote channels in a functionally relevant structure of the patient'sbrain, can also be used. Within the desired channel, the desireddetection tool (half wave, line length, area, or any other applicableactive technique) is selected (step 914); and the parameter is extractedfrom that detection tool's data storage (step 916). The parameterselected from a detection tool's storage can be representative of asignal's historical behavior, recent behavior in comparison to a trend,frequency content, or absolute value in comparison to a fixed or dynamicthreshold. Various possible observations derived from detection tooldata are described in detail in U.S. patent application Ser. No.09/896,092, filed on Jun. 28, 2001, which is hereby incorporated byreference as though set forth in full herein; these possibilities willbe apparent to a practitioner of ordinary skill.

It will be recognized that the parameter can then be used as illustratedin connection with FIG. 8, namely, to select and modify a course oftherapy to effectively treat a detected seizure onset or otherneurological event.

FIG. 10 illustrates how a parameter relating to an activeelectrophysiological measurement is obtained in some embodiments.Initially, if a new measurement is necessary (step 1010), e.g., if ithas been longer than a specified elapsed time since the lastelectrophysiological measurement, then an active measurement ofelectrophysiological characteristics is performed (step 1012). Aselectrophysiological measurements involve computation by theneurostimulator 110 and the delivery of stimulation signals (see U.S.patent application Ser. No. 09/706,322, referenced above), it isdesirable to perform a minimum number of measurements consistent withuseful information; accordingly, measurements are not performed if theyare not necessary.

The electrophysiological measurement results are then identified (step1014) and any desired parameter is then extracted therefrom (step 1016).For example, electrophysiological excitability, refractoriness, ortrends in either measurement may be used in some embodiments as thedesired parameter, and then employed according to the method set forthin FIG. 8.

Finally, FIG. 11 illustrates how a parameter related to a sensor signalis obtained in a system according to some embodiments.

As with the method of FIG. 10, if a new measurement is necessary (step1110), e.g., if it has been longer than a specified elapsed time sincethe last sensor measurement, then the desired sensor is queried and ameasurement is taken (step 1112). The processing of sensor measurementsgenerally involves computation by the neurostimulator 110, andaccordingly, it is desirable to perform a minimum number of sensormeasurements consistent with maintaining useful and timely information;accordingly, as with electrophysiology, sensor measurements are notperformed if they are not necessary.

The relevant sensor measurement results are then identified (step 1114),any desired parameter is then extracted therefrom (step 1116), and themeasurement, trend, or historical pattern is then used in variousembodiments as the desired parameter, and then employed according to themethod set forth in FIG. 8.

Reference in the specification to “one embodiment”, “an embodiment”,“various embodiments” or “some embodiments” means that a particularfeature, structure, or characteristic described in connection with theseembodiments is included in at least one embodiment of the invention, andsuch references in various places in the specification are notnecessarily all referring to the same embodiment.

It should be observed that while the foregoing detailed description ofvarious embodiments is set forth in some detail, the invention is notlimited to those details and an implantable neurostimulator orneurological disorder detection device made according to the inventioncan differ from the disclosed embodiments in numerous ways. Inparticular, it will be appreciated that embodiments may be employed inmany different applications to effectively treat different types ofseizure onsets and other neurological events. It will be appreciatedthat the functions disclosed herein as being performed by hardware andsoftware, respectively, may be performed differently in an alternativeembodiment. It should be further noted that functional distinctions aremade above for purposes of explanation and clarity; structuraldistinctions in a system or method according to the invention may not bedrawn along the same boundaries. Hence, the appropriate scope hereof isdeemed to be in accordance with the claims as set forth below.

What is claimed is:
 1. An implantable medical device system comprising:an implantable medical device configured to acquire EEG signals from apatient and to store a representation of the EEG signals in a memory; anexternal component provided with a software operating program andassociated hardware and configured to process, store, playback anddisplay on a display of the external component the representation of theEEG signals stored in the memory of the implantable medical device; anda communication link configured to establish communication between acommunications subsystem of the implantable medical device and theexternal component to enable the external component to process, store,playback and display on the display of the external component therepresentation of the EEG signals acquired and stored in the implantablemedical device.
 2. The implantable medical device system of claim 1wherein the communication link is a wireless link configured using ashort distance first link between the implantable medical device and atransceiver, and the transceiver is configured to relay communicationsbetween the implantable medical device and the external component. 3.The implantable medical device system of claim 1 wherein thecommunication link is a wireless link configured using a long distancefirst link between the implantable medical device and a transceiver, andthe transceiver is configured to relay information between theimplantable medical device and the external component.
 4. Theimplantable medical device system of claim 1 wherein the implantablemedical device is further configured to acquire informationcorresponding to signal activity sensed by at least one sensor inoperable communication with the implantable medical device, and thesoftware operating program further is configured to simulate thedetection and prediction of sensor signal activity representative ofmovement disorders based on a predetermined template developed for thepatient.
 5. The implantable medical device system of claim 1 wherein theimplantable medical device is further configured with at least oneanalysis tool configured to derive parameters from the EEG signalsassociated with at least one predetermined event and, if any parametersare derived, to store each parameter in the memory of the implantablemedical device together with the representation of the EEG signals, andthe software operating program and associated hardware of the externalcomponent is further configured to process, store, playback and displayon the display of the external component at least the representation ofthe EEG signals and any predetermined event detected in the EEG signalsbased on the derived parameters.
 6. The implantable medical devicesystem of claim 1 wherein the implantable medical device is furtherconfigured with at least one analysis tool configured to deriveparameters from one or more of the EEG signals or a state of theimplantable medical device when the EEG signals are acquired and, if anyparameters are derived, to store each parameter in the memory of theimplantable medical device together with the representation of the EEGsignals, and the software operating program and associated hardware ofthe external component is further configured to process, store, playbackand display on the display of the external component at least therepresentation of the EEG signals and any derived parameters.
 7. Theimplantable medical device system of claim 6 wherein the display of anyderived parameters on the external component may be directly associatedwith the display of the representation of the EEG signals.
 8. Theimplantable medical device system of claim 6 wherein the display of anyderived parameters on the display of the external component may beindirectly associated with the display of the representation of the EEGsignals.
 9. The implantable medical device system of claim 1, theimplantable medical device further configured with: a detectionsubsystem provided with at least one analysis tool configured to deriveone or more parameters from the EEG signals associated with at least onepredetermined event; a therapy subsystem provided with at least one of atherapeutic stimulator, a sensory stimulator, and a diagnosticstimulator, wherein each of the therapeutic stimulator, the sensorystimulator and the diagnostic stimulator is configured to deliver a formof neuromodulation to the neural tissue of a patient, the form ofneuromodulation characterized by one or more therapy parameters; amemory subsystem including the memory in which the representation of theEEG signals is stored and other memory in which the derived parameters,if any, and the therapy parameters, if any, are stored, and the softwareoperating program and associated hardware of the external component isfurther configured to process, store, playback and display on thedisplay of the external component at least the representation of the EEGsignals, any predetermined event detected in the EEG signals based onthe derived parameters, if any, and the form of neuromodulationdelivered, if any, based on the therapy parameters.
 10. The implantablemedical device system of claim 9, further comprising an adaptivesubsystem configured to do one of the following based on one or morederived parameters, if any: correlate or decorrelate the form ofneuromodulation therapy based on one or more of the derived parameters.11. A method of communicating information between an implantableneurostimulator and at least one external component configured toprocess, store, playback and display on a display of the externalcomponent a representation of EEG signals acquired and stored in theimplantable neurostimulator, comprising: acquiring signal activity fromthe patient's brain from at least one sensor, the at least one sensor inoperable communication with the implantable neurostimulator; processingthe signal activity with the implantable neurostimulator to provide adigital representation of the signal activity; storing the digitalrepresentation of the signal activity in an area of memory in a memorysubsystem of the implantable neurostimulator; establishing acommunication link between the implantable neurostimulator and theexternal component and communicating through the communication link thedigital representation of the signal activity from the area of memory tothe external component; and with a software operating program andassociated hardware of the external component, processing and displayingon a display of the external component the representation of the signalactivity.